The present invention relates to a novel pharmacological treatment of scleroderma SSc. There are different types of scleroderma. The multi-systemic fibrotic form, also called systemic sclerosis, comprises two sub-types depending on the degree of skin involvement: The limited cutaneous form affects the extremities whereas the diffuse subtype also involves the trunk. Besides the systemic disease, there are localized forms of the disease including e.g. morphea, that involve certain areas of the skin, sometimes joints and muscles, but not the internal organs. The major hallmarks of systemic sclerosis are widespread microvascular damage and progressive fibrosis of the skin and internal organs. The most evident clinical symptom is usually the hardening of the skin and associated scarring. The skin may appear tight, reddish or scaly. Despite the progress in managing complications which occur mostly due to organ failure, to date, there is still neither cure nor disease-specific treatment. Even though some currently available drugs may soften the skin and reduce inflammation, there is clearly a need for additional and efficacious medicaments for the treatment of scleroderma.
miR-29 is a small non-coding micro RNA that is involved in regulating gene expression. Animal miRNAs are transcribed as an approximately 70 nucleotide precursor and subsequently processed by the Dicer enzyme to give a product with approximately 22 nucleotides. In this case the mature sequence comes from the 3′ end of the precursor RNA. The products are thought to have regulatory roles through complementarity to the 5′ end of the target mRNA. To the miR-29 family belong miR-29a, miR-29b1 and miR29b2, and miR-29c.
It has been shown that miR-29 regulates the level of the Mcl-1 protein, an anti-apoptotic member of the Bcl-2 family of proteins. Furthermore it has been shown that miR-29 regulates the level of Tcl1 protein, an oncogene found to be disrupted in many T-cell leukemias, and directly targets both DNMT3A and DNMT-3B which are frequently upregulated in lung cancer. Furthermore it has been shown that in the absence of miR-208, miR-29 expression is upregulated, preventing cardiac fibrosis (WO 2008/074866). The role of miR-29 in skin cells and in scleroderma has so far not been investigated.